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Structural And Functional Investigation Of The Interaction Of Agomelatine With Model MembranesErgun, Seza 01 October 2012 (has links) (PDF)
Depression is one of the most commonly seen psychiatric diseases in the population
in recent years. Treatment of depression is mainly carried out by psychiatric drugs. In
the past few years, agomelatine which is released to the market with a trade name,
Valdoxane, has been thought to have far less side effects due to its non-addictive
nature, not having trouble when the drug is quitted, and also due to its property of
binding only to the specific receptor that the drug interacts with. The action
mechanism of agomelatine on the membrane structure has not been clarified yet, for
instance, no study has been found in the literature about the interaction of agomelatin
with the lipids of biological membranes. In this current study, the interaction of
agomelatine with the model membranes of dipalmitoylphosphatidylcholine (DPPC),
dipalmitoylphosphatidylgylcerol (DPPG) and sphingomyelin (SM) is examined by
Fourier transform infrared spectroscopy (FTIR) and Differential scanning
calorimetry (DSC).
DSC and FTIR studies show that, agomelatine shifts the phase transition temperature
of DPPC and DPPG multilamellar membrane to the lower degrees, however, it shifts
the phase transition temperature of SM membrane to the higher degrees.
Agomelatine addition increases the lipid order of the DPPC and SM liposome,
whereas, it decreases the lipid order of DPPG liposome. Moreover this drug
enhances the membrane fluidity among all types of liposome studied. The increase of
v
lipid order and increase of fluidity at DPPC and SM liposome indicates domain
formation upon drug addition (Vest et al., 2004). This was also confirmed by DSC
studies.
Agomelatine enhances H bonding capacity of all types of liposomes have been
studied. However it has different effects on glycerol backbones of the DPPC and
DPPG liposomes. At low agomelatine concentrations the increase in the frequency
values indicates a decrease in the hydrogen bonding capacity of the glycerol skeleton
of DPPC. In contrast, at high concentrations of agomelatine, a decrease in the
frequency values was observed as an indicator of the enhancement of the hydrogen
bonding capacity. So it enhances H-bonding capacity at gel phase but lowers it at
liquid chrystalline phases. A progressive decreases in Tm was observed at DPPG and
DPPC liposomes where it increased the Tm at SM. The pretransition peak is
abolished and the Tm peak becomes broad, indicating a larger perturbation to the
membrane. These observations indicate the possible interaction of agomelatine with
the head group as well. The shoulder seen at the thermograms of DPPC and DPPC
liposomes at high doses may indicate the lateral phase separation in to drug-rich and
drug-poor domains (D&rsquo / Souza et al., 2009). These results may indicate that
agomelatine is partially buried in the hydrocarbon core of the bilayer, interacting
primarily with the C2-C8 methylene region of the hydrocarbon chains. All these
results highlight the fact that agomelatine interacts around the head group in such a
manner that it destabilizes the membrane architecture to a large extent.
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Effect Of Hydrogenation Conditions On Rheological And Micro-structural Properties Of FatsBaskocak, Altug 01 September 2011 (has links) (PDF)
Hydrogenation is one of the most applied techniques in the fats and oils industry to produce wide range of hardened fats with different physical and chemical properties. Each different combination of hydrogenation conditions serves products of different rheological and micro-structural properties. Therefore, the purpose of this study is to examine the effect of different industrially available catalysts on rheological and micro-structural properties of hydrogenated fats.
Three different catalysts were used at two different concentrations to hydrogenate soybean oil. Two nickel based (Nysosel 222 and SP 10) and one palladium based (Pd/Al2O3) catalyst were employed. Each oil sample was hydrogenated for 20, 40, 60, 80 and 100 minutes of time intervals, under 165 º / C temperature, 2 bar H2 pressure and 500 rpm stirring rate. Resulting hardened fat samples were analysed in terms of rheological and microstructural properties.
The outcomes of rheological and micro-structural analyses had a strong resemblence with the fatty acid distributions, solid fat contents, slip melting points and iodine values of the samples. The most selective catalyst was SP10, with the products of the highest trans fatty acid concent and more solid-like / where the least selective one was Pd/A with lowest trans fatty acid content and least solid-like. Crystal number and properties, the behaviours of storage and loss moduli were in correlation with trans fatty acid content of the samples. Also the moduli had a considerable parallelity with solid fat contents.
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